Highly polarized Th17 cells induce EAE via a T-bet independent mechanism

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Abstract

In the MOG35-55 induced EAE model, autoreactive Th17 cells that accumulate in the central nervous system acquire Th1 characteristics via a T-bet dependent mechanism. It remains to be determined whether Th17 plasticity and encephalitogenicity are causally related to each other. Here, we show that IL-23 polarized T-bet-/- Th17 cells are unimpaired in either activation or proliferation, and induce higher quantities of the chemokines RANTES and CXCL2 than WT Th17 cells. Unlike their WT counterparts, T-bet-/- Th17 cells retain an IL-17hiIFN-γneg-lo cytokine profile following adoptive transfer into syngeneic hosts. This population of highly polarized Th17 effectors is capable of mediating EAE, albeit with a milder clinical course. It has previously been reported that the signature Th1 and Th17 effector cytokines, IFN-γ and IL-17, are dispensable for the development of autoimmune demyelinating disease. The current study demonstrates that the "master regulator" transcription factor, T-bet, is also not universally required for encephalitogenicity. Our results contribute to a growing body of data showing heterogeneity of myelin-reactive T cells and the independent mechanisms they employ to inflict damage to central nervous system tissues, complicating the search for therapeutic targets relevant across the spectrum of individuals with multiple sclerosis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Grifka-Walk, H. M., Lalor, S. J., & Segal, B. M. (2013). Highly polarized Th17 cells induce EAE via a T-bet independent mechanism. European Journal of Immunology, 43(11), 2824–2831. https://doi.org/10.1002/eji.201343723

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